Involvement of Endoplasmic Reticulum Stress, Autophagy and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury

Chiang, Chih‐Kang; Wang, Ching-Chia; Lu, Tien-Fong; Huang, Kuo-How; Sheu, Meei-Ling; Liu, Shing‐Hwa; Hung, Kuan‐Yu

doi:10.1038/srep34167

Cited by 49 publications

(37 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…60,61 More recently, it has also been implicated in peroxisome biogenesis 62,63 and regulation of the cellular process autophagy. 35,36,55,64,65 These studies suggest a wide range of possible activities by 4-PBA that are highly dependent on the cell type, dosage, and treatment regime. However, as alluded to previously, very few of these studies have been conducted in the context of macrophage polarization by LPS.…”

Section: Discussionmentioning

confidence: 93%

Phenylbutyrate facilitates homeostasis of non-resolving inflammatory macrophages

et al. 2019

View full text Add to dashboard Cite

Non-resolving inflammatory monocytes/macrophages are critically involved in the pathogenesis of chronic inflammatory diseases. However, mechanisms of macrophage polarization are not well understood, thus hindering the development of effective strategies to promote inflammation resolution. In this study, we report that macrophages polarized by subclinical super-low dose LPS preferentially expressed pro-inflammatory mediators such as ccl2 (which encodes the protein monocyte chemo attractant protein-1) with reduced expression of anti-inflammatory/homeostatic mediators such as slc40a1 (which encodes the protein ferroportin-1). We observed significantly elevated levels of the autophagy-associated and pro-inflammatory protein p62 in polarized macrophages, closely correlated with the inflammatory activation of ccl2 gene expression. In contrast, we noted a significant increase of ubiquitinated/inactive nuclear-erythroid-related factor 2 (NRF2), consistent with reduced slc40a1 gene expression in polarized macrophages. Addition of the homeostatic restorative agent phenylbutyrate (4-PBA) effectively reduced cellular levels of p62 as well as ccl2 gene induction by super-low dose LPS. On the other hand, application of 4-PBA also blocked the accumulation of ubiquitinated NRF2 and restored anti-inflammatory slc40a1 gene expression in macrophages. Together, our study provides novel insights with regard to macrophage polarization and reveals 4-PBA as a promising molecule in restoring macrophage homeostasis.

show abstract

Section: Discussionmentioning

confidence: 93%

Phenylbutyrate facilitates homeostasis of non-resolving inflammatory macrophages

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Because ER stress plays important roles in osteoblast apoptosis and osteoporosis, (15,25) we hypothesized that intracellular AGEs induced osteoblast apoptosis via ER stress. Therefore, we examined the effect of GA on ER stress signaling in MC3T3-E1 cells.…”

Section: Involvement Of Er Stress With Ga-induced Age Accumulation Wimentioning

confidence: 99%

“…(13) Recent reports have shown that extracellular AGEs induce apoptosis via ER stress in diverse cell types. (14,15) However, little is known regarding the effects of intracellular AGEs on the activation of ER stress in osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Accumulation of Advanced Glycation End Products Induces Osteoblast Apoptosis Via Endoplasmic Reticulum Stress

Suzuki

Fujiwara

Saito

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Osteoporosis is an aging-associated disease that is attributed to excessive osteoblast apoptosis. It is known that the accumulation of advanced glycation end products (AGEs) in bone extracellular matrix deteriorates osteoblast functions. However, little is known about the interaction between intracellular AGE accumulation and the induction of osteoblast apoptosis. In this study, we investigated the effect of intracellular AGE accumulation on osteoblast apoptosis in vitro and in vivo. In vitro, murine osteoblastic MC3T3-E1 cells were treated with glycolaldehyde (GA), an AGE precursor. GA-induced intracellular AGE accumulation progressed in time-and dosedependent manners, followed by apoptosis induction. Intracellular AGE formation also activated endoplasmic reticulum (ER) stress-related proteins (such as glucose-regulated protein 78, inositol-requiring protein-1α (IRE1α), and c-Jun N-terminal kinase) and induced apoptosis. In agreement, treatment with the ER stress inhibitor 4-phenylbutyric acid and knocking down IRE1α expression ameliorated osteoblast apoptosis. Furthermore, the ratio between AGE-and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive osteoblasts in human vertebral bodies was significantly higher in an elderly group than in a younger group. A positive linear correlation between the ratio of AGE-positive and TUNEL-positive osteoblasts (r = 0.72) was also observed. Collectively, these results indicate that AGEs accumulated in osteoblasts with age and that intracellular AGE accumulation induces apoptosis via ER stress. These findings offer new insight into the mechanisms of osteoblast apoptosis and age-related osteoporosis.

show abstract

“…Le transforming growth factor b (TGF), une cytokine profibrosante ayant un rôle important dans la physiopathologie de la glomérulosclérose, induit l'autophagie dans les cellules mésangiales réduisant la production de matrice mésangiale en initiant la dégradation de collagène de type I, un effet a priori bénéfique de l'autophagie dans le processus [34]. Le flux autophagique peut également être activé dans les cellules mésangiales en réponse à la production d'AGE, mais les conséquences de ce processus sur le développement de la néphropathie diabétique restent inconnues [35].…”

Section: Autophagie Rénaleunclassified

Autophagie rénale

Pallet

2017

Med Sci (Paris)

View full text Add to dashboard Cite

Autophagy is a highly conserved, physiological, catabolic process, involving the lysosomal degradation of cytosolic components, including macromolecules (such as proteins and lipids) and cytosolic organelles. Autophagy is believed to be essential for the maintenance of cellular homeostasis, for a number of fundamental biological activities, and an important component of the complex response of cells to multiple forms of stress. Autophagy is involved in the pathogenesis of a number of clinically important disorders but, until recently, little was known about its connection to kidney diseases. However, there is now growing evidence that autophagy is specifically linked to the pathogenesis of important renal diseases such as acute kidney injury, diabetic nephropathy and polycystic kidney disease. However, an understanding of the precise role of autophagy in the course of kidney diseases is still in its infancy. The review points out areas of particular interest for future research, and also discusses the importance of such information on whether the pharmacologic agents that modulate autophagy are potentially usable as novel forms of treatment for various kidney diseases.

show abstract

Involvement of Endoplasmic Reticulum Stress, Autophagy and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury

Cited by 49 publications

References 53 publications

Phenylbutyrate facilitates homeostasis of non-resolving inflammatory macrophages

Phenylbutyrate facilitates homeostasis of non-resolving inflammatory macrophages

Intracellular Accumulation of Advanced Glycation End Products Induces Osteoblast Apoptosis Via Endoplasmic Reticulum Stress

Autophagie rénale

Contact Info

Product

Resources

About